| Abstract: | Intracellular potassium ion (K+) in cultured human fibroblasts (HF cells) was maintained at reduced steady-state levels by incubating cells in various ouabain concentrations. Small decreases in cell K+ had no effect on protein synthesis and cell growth, but when cell K+ fell below 60–80% of control levels, the rate of protein synthesis decreased in proportion to further reductions in K+. DNA synthesis was also inhibited, presumably because of its dependence on protein synthesis. On the other hand, RNA synthesis remained uninhibited over a wide range of K+ concentrations, an effect characteristic of many specific inhibitors of protein synthesis.In ouabain-treated cells neither levels of ATP nor transport of amino acids was limiting for protein synthesis. Loss of activity of messenger or other species of RNA was not responsible for inhibition of protein synthesis, since in the presence of actinomycin D, the rate of protein synthesis could be decreased or increased solely by adjusting cell K+. Release from ouabain inhibition restored K+ levels, macromolecular synthesis, and cell growth, but there was no resulting synchrony of cell division. In cell populations partially synchronized by serum starvation and refeeding protein synthesis was sensitive to reduction in K+ levels throughout the cell cycle.Our quantitative results show that cell K+ levels, when sufficiently reduced, can determine the rate of protein synthesis and hence the rate of cell growth. |
